Integrated cryogenic electron microscopy (cryoEM) and cryogenic electron tomography (cryoET) approach, advanced through NSF’s STROBE, a National Science Foundation Science and Technology Center, enables unparalleled resolution for complex cellular structures like the flagellar doublet microtubules (DMT) of Trypanosoma brucei. This parasite causes African sleeping sickness, affecting millions. The flagellum is essential for motility, infectivity, and survival across different host environments. STROBE-supported cryoEM at the EICN resource at UCLA allowed high-resolution imaging of native structures, bypassing artifacts of recombinant systems and revealing detailed architecture of the 96-nm repeat with 154 proteins, including 40 parasite-specific ones (see figure).
The study provides critical insights into motility mechanisms by capturing axonemal dynein motors in the pre-power stroke conformation. This supports a novel ‘dragon boat’ model in which coordinated power strokes of dyneins drive microtubule sliding, generating the characteristic helical waveform that powers parasite movement through blood and tissues. Significantly, dyneins are the molecular motor across all living cells, including ours, and the mechanisms are universal.
This STROBE-supported, NSF-funded cryoEM study elucidates the mechanochemical basis of flagellar motility, offering new avenues for therapeutic intervention against trypanosomatid diseases and advancing our understanding of eukaryotic flagella evolution and function.